Effect of Oral Lactate Administration on Skeletal Muscle Mass in Mice Under Different Loading Conditions.

Background/aim: Lactate is a physiologically active substance secreted by skeletal muscle that has been suggested to stimulate muscle mass gain. However, the molecular mechanism for lactate-associated muscle hypertrophy remains unclear. The purpose of the present study was to investigate whether oral administration of lactate increases muscle mass under different loading conditions.

Mannose-methyl-β-cyclodextrin suppresses tumor growth by targeting both colon cancer cells and tumor-associated macrophages.

Methylated β-cyclodextrin (MβCD) can extract cholesterol from lipid rafts and induce apoptosis in cancer cells by inhibiting activation of the PI3K-Akt-Bad pathway. In this study, we modified MβCD with mannose (Man-MβCD) and assessed its in vitro and in vivo potential for targeting colon cancer cells expressing the mannose receptor (MR) and tumor-associated macrophages (TAM). Man-MβCD showed a significantly greater level of cellular association with colon-26 cells and M2 macrophages, and much more prominent anticancer activity than that of MβCD against MR-positive colon-26 cells.

Antigen stabilizing hydrogels based on cyclodextrins and polyethylene glycol act as type-2 adjuvants with suppressed local irritation.

Recent viral pandemics have increased global demand for vaccines. However, the supply of effective and safe vaccine not only to developed countries but also developing countries with inadequate storage equipment is still challenging due to the lack of robust systems which improve the efficacy and the stability of vaccines with few side effects. In our previous study, polypseudorotaxane (PPRX) hydrogels based on cyclodextrin (CyD) and polyethylene glycol (PEG) significantly improved the stability of antibody preparations and showed no serious adverse effects after subcutaneous injection, suggesting the possibility as safe vaccine formulations to stabilize an antigen protein.

Improvement of Pharmaceutical Properties of Zerumbone, a Multifunctional Compound, Using Cyclodextrin Derivatives.

Zerumbone is a multifunctional compound which shows various biological activities, such as antitumor activity, anti-inflammatory activity, antiulcer activity, etc. However, to use Zerumbone as functional foods or medicines, its pharmaceutical properties such as solubility should be improved. In the present study, we prepared its inclusion complexes with various cyclodextrin (CyD) derivatives, and evaluated their solubility, release profile of the drug and cytotoxic activity.

Lactose-appended β-cyclodextrin as an effective nanocarrier for brain delivery.

The blood-brain barrier (BBB) prevents the permeability of drugs into the brain, and as such limits the management of various brain diseases. To overcome this barrier, drug-encapsulating nanoparticles or vesicles, drug conjugates, and other types of drug delivery systems (DDSs) have been developed. However, the brain-targeting ability of nanoparticles or vesicles is still insufficient.

MBNL1-Associated Mitochondrial Dysfunction and Apoptosis in C2C12 Myotubes and Mouse Skeletal Muscle.

We explored the interrelationship between a tissue-specific alternative splicing factor muscleblind-like 1 (MBNL1) and peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α), B-cell lymphoma 2 (Bcl-2) or Bcl-2-associated X protein (Bax) in C2C12 myotubes and mouse skeletal muscle to investigate a possible physiological role of MBNL1 in mitochondrial-associated apoptosis of skeletal muscle. Expression level of PGC-1α and mitochondrial membrane potential evaluated by the fluorescence ratio of JC-1 aggregate to monomer in C2C12 myotubes were suppressed by knockdown of MBNL1. Conversely, the ratio of Bax to Bcl-2 as well as the apoptotic index in C2C12 myotubes was increased by MBNL1 knockdown.

The Protective Effect of Brazilian Propolis against Glycation Stress in Mouse Skeletal Muscle.

We investigated the protective effect of Brazilian propolis, a natural resinous substance produced by honeybees, against glycation stress in mouse skeletal muscles. Mice were divided into four groups: (1) Normal diet + drinking water, (2) Brazilian propolis (0.1%)-containing diet + drinking water, (3) normal diet + methylglyoxal (MGO) (0.

Lactate Stimulates a Potential for Hypertrophy and Regeneration of Mouse Skeletal Muscle.

The effects of lactate on muscle mass and regeneration were investigated using mouse skeletal muscle tissue and cultured C2C12 cells. Male C57BL/6J mice were randomly divided into (1) control, (2) lactate (1 mol/L in distilled water, 8.9 mL/g body weight)-administered, (3) cardio toxin (CTX)-injected (CX), and (4) lactate-administered after CTX-injection (LX) groups.

DAMP-Inducing Adjuvant and PAMP Adjuvants Parallelly Enhance Protective Type-2 and Type-1 Immune Responses to Influenza Split Vaccination.

Recently, it was reported that 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD), a common pharmaceutical additive, can act as a vaccine adjuvant to enhance protective type-2 immunogenicity to co-administered seasonal influenza split vaccine by inducing host-derived damage-associated molecular patterns (DAMPs). However, like most other DAMP-inducing adjuvants such as aluminum hydroxide (Alum), HP-β-CyD may not be sufficient for the induction of protective type-1 (cellular) immune responses, thereby leaving room for improvement. Here, we demonstrate that a combination of HP-β-CyD with a humanized TLR9 agonist, K3 CpG-ODN, a potent pathogen-associated molecular pattern (PAMP), enhanced the protective efficacy of the co-administered influenza split vaccine by inducing antigen-specific type-2 and type-1 immune responses, respectively.

Activation of adiponectin receptors has negative impact on muscle mass in C2C12 myotubes and fast-type mouse skeletal muscle.

This study investigated the effects of AdipoRon, which is an agonist for adiponectin receptor 1 (AdipoR1) and AdipoR2, on the protein content, myotube diameter, and number of nuclei per myotube of C2C12 cells and skeletal muscle mass in C57BL/6J mice. AdipoRon suppressed the protein content, myotube diameter, and number of nuclei per myotube of C2C12 cells of C2C12 myotubes in a dose-dependent manner. Adiponectin-associated decline of protein content, diameter, and number of nuclei per myotube in C2C12 myotubes was partially rescued by knockdown of AdipoR1 and/or AdipoR2.

AMPK Mediates Muscle Mass Change But Not the Transition of Myosin Heavy Chain Isoforms during Unloading and Reloading of Skeletal Muscles in Mice.

5'AMP-activated protein kinase (AMPK) plays an important role in the regulation of skeletal muscle mass and fiber-type distribution. However, it is unclear whether AMPK is involved in muscle mass change or transition of myosin heavy chain (MyHC) isoforms in response to unloading or increased loading. Here, we checked whether AMPK controls muscle mass change and transition of MyHC isoforms during unloading and reloading using mice expressing a skeletal-muscle-specific dominant-negative AMPKα1 (AMPK-DN).

Potential involvement of dietary advanced glycation end products in impairment of skeletal muscle growth and muscle contractile function in mice.

Diets enriched with advanced glycation end products (AGE) have recently been related to muscle dysfunction processes. However, it remains unclear whether long-term exposure to an AGE-enriched diet impacts physiological characteristics of skeletal muscles. Therefore, we explored the differences in skeletal muscle mass, contractile function and molecular responses between mice receiving a diet high in AGE (H-AGE) and low in AGE (L-AGE) for 16 weeks.

Suppression of Myostatin Stimulates Regenerative Potential of Injured Antigravitational Soleus Muscle in Mice under Unloading Condition.

Effects of myostatin (MSTN)-suppression on the regeneration of injured skeletal muscle under unloading condition were investigated by using transgenic mice expressing a dominant-negative form of MSTN (MSTN-DN). Both MSTN-DN and wild-type (WT) mice were subjected to continuous hindlimb suspension (HS) for 6 weeks. Cardiotoxin (CTX) was injected into left soleus muscle under anesthesia 2 weeks after the initiation of HS.

Microcurrent electrical neuromuscular stimulation facilitates regeneration of injured skeletal muscle in mice.

Conservative therapies, mainly resting care for the damaged muscle, are generally used as a treatment for skeletal muscle injuries (such as muscle fragmentation). Several past studies reported that microcurrent electrical neuromuscular stimulation (MENS) facilitates a repair of injured soft tissues and shortens the recovery period. However, the effects of MENS on the regeneration in injured skeletal muscle are still unclear.

Loading-associated expression of TRIM72 and caveolin-3 in antigravitational soleus muscle in mice.

Effects of mechanical loading on the expression level of tripartite motif-containing 72 (TRIM72) and caveolin-3 (Cav-3) in mouse soleus muscle were investigated. Mice were subjected to (1) continuous hindlimb suspension (HS) for 2 weeks followed by 1-week ambulation recovery or (2) functional overloading (FO) on the soleus by cutting the distal tendons of the plantaris and gastrocnemius muscles. Soleus muscle atrophy was induced by 2-week hindlimb suspension (HS).

AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C2C12 skeletal muscle cells.

5'-AMP-activated protein kinase (AMPK) plays an important role as a negative regulator of skeletal muscle mass. However, the precise mechanism of AMPK-mediated regulation of muscle mass is not fully clarified. Heat shock proteins (HSPs), stress-induced molecular chaperones, are related with skeletal muscle adaptation, but the association between AMPK and HSPs in skeletal muscle hypertrophy is unknown.

Up-regulation of adiponectin expression in antigravitational soleus muscle in response to unloading followed by reloading, and functional overloading in mice.

The purpose of this study was to investigate the expression level of adiponectin and its related molecules in hypertrophied and atrophied skeletal muscle in mice. The expression was also evaluated in C2C12 myoblasts and myotubes. Both mRNA and protein expression of adiponectin, mRNA expression of adiponectin receptor (AdipoR) 1 and AdipoR2, and protein expression of adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif 1 (APPL1) were observed in C2C12 myoblasts.

Regeneration of injured skeletal muscle in heat shock transcription factor 1-null mice.

The purpose of this study was to investigate a role of heat shock transcription factor 1 (HSF1)-mediated stress response during regeneration of injured soleus muscle by using HSF1-null mice. Cardiotoxin (CTX) was injected into the left muscle of male HSF1-null and wild-type mice under anesthesia with intraperitoneal injection of pentobarbital sodium. Injection of physiological saline was also performed into the right muscle.

Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle.

Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1), and up-regulate heat shock proteins (HSPs) in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading.

Microcurrent electrical nerve stimulation facilitates regrowth of mouse soleus muscle.

Microcurrent electrical nerve stimulation (MENS) has been used to facilitate recovery from skeletal muscle injury. However, the effects of MENS on unloading-associated atrophied skeletal muscle remain unclear. Effects of MENS on the regrowing process of unloading-associated atrophied skeletal muscle were investigated.

Effects of heat stress on muscle mass and the expression levels of heat shock proteins and lysosomal cathepsin L in soleus muscle of young and aged mice.

Effects of heat stress on skeletal muscle mass in young and aged mice were investigated. Young (7-week) and aged (106-week) male C57BL/6J mice were randomly assigned to control and heat-stressed groups in each age. Mice in heat-stressed group were exposed to heat stress (41 °C for 60 min) in an incubator without anesthesia.

Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission.

The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5-20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight.

Absence of heat shock transcription factor 1 retards the regrowth of atrophied soleus muscle in mice.

Effects of heat shock transcription factor 1 (HSF1) gene on the regrowth of atrophied mouse soleus muscles were studied. Both HSF1-null and wild-type mice were subjected to continuous hindlimb suspension for 2 wk followed by 4 wk of ambulation recovery. There was no difference in the magnitude of suspension-related decrease of muscle weight, protein content, and the cross-sectional area of muscle fibers between both types of mice.

Possible role of NF-ĸB signals in heat stress-associated increase in protein content of cultured C2C12 cells.

Heat stress is one of the hypertrophic stimuli on mammalian skeletal muscle. Nuclear factor-κB (NF-κB) signaling plays an important role in the regulation of skeletal muscle mass. However, the effects of heat stress on NF-κB signaling in skeletal muscle cells remain unclear.